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Suppression of in vitro antibody response by spleen cells of mice infected with Friend-associated lymphatic leukemia virus.

The ability of spleen cells of mice infected with oncornaviruses to depress the in vitro antibody responsiveness of normal lymphoid cells was exploited in an attempt to clarify the role played by the lymphatic leukemia virus (LLV) component in the immunodepressive properties of the Friend leukemia complex. Spleen cells of mice infected with LLV or, for comparison, with the entire complex were added to cultures of sheep erythrocyte-primed uninfected spleen cells, and the antibody-forming cells produced by the latter, after antigen restimulation, were assayed. The addition within 2 days from culture initiation of low numbers of cells infected with either virus preparation suppressed all stages of the response affecting the production of both immunoglobulin M and immunoglobulin G antibody. The activity of infected cells resisted doses of ultraviolet radiation which inhibit cell multiplication but was abolished by disrupting the cells and was prevented by the presence of anti-LLV antibodies. The LLV-infected spleen cells responsible for suppression were not removed by treatments which selectively remove or kill macrophages and exhibited surface properties of B lymphocytes. These results were interpreted as indicating that the effect is due to virus (or viral products) released by B cells. The suppressing cells in the spleens of mice in the early days of Friend leukemia complex infection presented superimposable properties, supporting the concept that their activity is also due to the LLV they release in large quantities. However, in later stages of infection, the spleens of Friend leukemia complex-infected mice also contained non-B-suppressing cells possibly derived from the proliferation of nonlymphoid LLV-producing cells caused by the neoplastic process.

Animals

Computed tomography in white-matter disease.

CT scans of 11 patients with proved white-matter disease were reviewed and divided into three categories. The demyelinating (secondary) and diffuse sclerosis groups frequently exhibited abnormal intravenous enhancement and mass shift. This made differentiation from inflammatory and neoplastic processes difficult. In the dysmyelinating disorders, pathologically noted diffuse loss of white matter and absence of inflammatory response appeared on the scans as areas of diffuse and decreased density in the centrum semiovale. There was no evidence of abnormal contrast enhancement.

Adult

Model systems for the study of prostatic cancer.

Application of suitable in vivo and in vitro model systems are necessary to further investigations in prostatic adenocarcinoma. Model systems are defined, and discussed in terms of their potential application to the study of the neoplastic process.

Adenocarcinoma

[ Correlation between histopathologic and scintigraphic findings (employing 67Ga) in relation to the surgical indication for bronchial carcinoma (author's transl)].

Following the investigation on the correlation between scintigraphic pictures and histopathologic findings in 66 patients with suspected bronchial carcinoma, 84% of the scannings were positive and the data relative to the so-called "false negative" cases was analyzed. The presence of hilar or mediastinal lymph node metastases, histologically ascertained in about one-third of the patients, appeared significant; and a restricted accumulation of the radio-element was evident in 70.5% of the cases. In 10 of the cases with negative scintigraphic findings, pictures of reactive or hyperplastic lymphadenitis (almost all radiologically relievable) were obtained. Therefore, if it cannot be logically concluded that the negative scintigraphic findings at the mediastinal level indicate the absence of metastases in the lymph nodes, thus indicating surgery (or preventive mediastinoscopy), positive finding seem to be synonymous with extrapulmonary diffusion of the neoplastic process, with direct implication in determining the operability of the patient.

Bronchial Neoplasms

Infiltrating neoplasms of the kidney.

Some neoplastic processes which involve the kidney develop not as a distinct localized mass, but rather as an infiltrating process which replaces the renal parenchyma, causes little or no mass effect, and contains little if any neovascularity. These neoplasms include (1) carcinoma of the renal pelvis when it invades the parenchyma (transitional cell and squamous cell); (2) blood-borne metastatic squamous cell carcinoma to the kidney (most frequently from the lung): (3) renal lymphoma of the infiltrating variety; and (4) infiltrating sarcomatous type of hypernephroma. While the urographic and angiographic appearance of these infiltrating lesions can be similar, clinical aspects are usually sufficient to differentiate them. Radiographic findings include amputation of portions of the collecting system on urography and encasement of vessels with a loss of nephrogram on angiography.

Adenocarcinoma

Treatment of Paget's disease of bone with mithramycin.

The hypothesis that Paget's disease of bone is a low grade neoplastic process led us to use the cytotoxic antibiotic mithramycin in its treatment. The dramatic effects observed on the serum calcium and alkaline phosphatase, and urinary hydroxyproline are compatible with the concept that mithramycin is primarily toxic to osteoclasts. Subjective and objective clinical effects establish this agent as useful in the treatment of Paget's disease despite its observed toxicity to other organ systems.

Chemical and Drug Induced Liver Injury

Influence of carbon tetrachloride or riboflavin on liver carcinogenesis with a single dose of aflatoxin b1.

Liver carcinogenesis with a single dose of aflatoxin B1 (7 mg/kg body weight) has been investigated in a group of female Wistar strain rats by repeated biopsies and necropsies. Another group received a subsequent intoxication with carbon tetrachloride by inhalation (approximately 200 doses) and another one was overloaded with riboflavin (25 parts/10(6) in drinking water). The frequency of hepatomata was almost equal in the aflatoxin and aflatoxin-carbon tetrachloride group. It was lowere in the riboflavin-aflatoxin group. In these 3 groups cirrhosis was never present in neoplastic livers. Megalocytosis was the first lesion observed. All tumoral livers had previous or concomitant megalocytosis. This modification was about as frequent, intense and widespread in aflatoxin-CCl4 and aflatoxin groups but appeared much earlier, as did the first hepatoma, in the aflatoxin-CCl4 group. It was less frequent, less intense and less widespread in the riboflavin-aflatoxin group than in the aflatoxin group. There was also a lower frequency of hepatomata in the riboflavin-aflatoxin group, but the difference was not significant due to the too small number of animals involved. The facts are not a proof of the existence of an obligatory link between megalocytosis and carcinogenesis since a slight megalocytosis was observed in the riboflavin group not affected by the neoplastic process. However, the simplest explanation of our results would be to consider that the potential tumour cells are located among the megalocytic cells, without admitting that every megalocyte is obligatorily a precancerous cell. CCl4 seems to act in shortening the time of appearance of megalocytosis. The protective effect of riboflavine should be regarded with more caution.

Aflatoxins

[Etiological role of the herpes simplex virus in causing cervical cancer].

The results of the composite virological and immunological examinations of 46 patients with cervical carcinoma (CC) attest to the association of herpes simplex virus (HSV) with neoplastic processes. HSV strains were isolated from the tumour tissue as well as from the cervical canal secretions and blood of 4 patients. A higher level of virus-neutralizing and complement-fixing antibodies to HSV was found in sera from CC patients as compared with the control group of normal women. Antibody to HSV type 2 was found in 38.8% of sera from the patients and 12.6% in the control group. Lymphocytes from CC patients induced blasttransformation reaction to HSV twice as frequently as those from healthy subjects. The virus-specific antigen was found in tumour cells of 36% CC patients in immunofluorescent examinations of smears from the cervix. The presented results are related to the determination of the etiological role of HSV in cervical carcinoma.

Adult

Histological and histochemical studies of oral cancer.

Increasing attempts are now being made to measure and to assess the relative importance of histologic features in oral premalignant and malignant conditions in order to improve the accuracy of diagnosis and prognosis. Though certain individual features, such as DNA content of cell nuclei, or stereological parameters like nuclear : cytoplasmic ration or desmosome density can be very accurately quantified, no single feature can completely characterize the neoplastic process. Multifactorial studies are thus of great importance, even though it is not practicable to measure all the parameters included with the sam accuracy; in such studies retrospective computation of the relative importance of individual parameters is of greater value than arbitarily assigned weights. So far as early prediction of malignant transformation in oral premalignant lesions is concerned, great interest is now being shown in the reactivity of glucose-6-phosphate dehydrogenase in epithelial cells. For predicting the prognosis of patients with established squamous cell carcinoma of the mouth, it is now realized that thenature and intensity of the host immune inflammatory response seen in the connective tissue within the surrounding the tumour and in affected regional lymph nodes, is at least as important as are the features of the tumour cells themselves.

Cell Division

Antineoplaston A in cancer therapy. (I).

Twenty-one patients with advanced cancer or leukemia were treated with antineoplaston A and followed for up to nine months. Dosage by intravenous, intramuscular, subcutaneous, rectal, intrapleural, intravesical and/or topical administration ranged from 0.6 to 33 U/m2/24 h. Treatment was well tolerated, although side effects included fever of short duration and elevation of platelet and white blood count. In 18 cases some degree of clinical improvement was observed. Complete remission occurred in 4 cases. More than 50% remission occurred in 4 other cases which, along with another 6 cases, are continuing the treatment with high doses of antineoplaston A and show a continuing regression of the tumors although not yet achieving the criteria for complete remission; 2 of these 6 cases seem unlikely to achieve remission. Two patients temporarily discontinued treatment. During treatment, 5 patients expired; in 2 of them, however, was seen significant regression of the neoplastic process. The deaths were not due to cancer or to any toxicity incurred by the treatment.

Administration, Topical

Local reaction to gingival injections of MER/BCG in guinea pigs.

The local reaction to gingival injections of methanol extraction residue of BCG (MER/BCG) was investigated in guinea pigs to help determine the potential of this agent in treating oral carcinoma. The drug was used in a standard and diluted form. Both concentrations were well tolerated and caused no ulceration or necrosis. Histological examinations performed at predetermined intervals showed an inflammatory response to the standard and the diluted solution. This reaction was more pronounced when the higher concentration was used. No changes in the alveolar bone were found in either of the groups. Complete healing with scar formation was evident four to six weeks later. The absence of severe reactions after injections of MER should encourage further investigations of this agent in the local treatment of neoplastic processes in the oral cavity.

Animals

["Primary" reticulum-cellsarcoma of the retina. I. Clinico-pathologic study of 5 patients (author's transl)].

Between 1964 and 1974 a primary reticulum-cellsarcoma of the retina was diagnosed histologically in 5 patients (between 44 and 71 years), in one already clinically. The initial diagnosis had been "uveitis" (2), "panuveitis" (1), "iridocyclitis with central retinal artery occlusion" (1), and "chorioretinitis" (1). The usual antiinflammatory therapy was without effect in every instance. All patients showed neurological symptoms with cerebral manifestations. Twice the cerebral biopsies had been misinterpreted initially as "atypical glioblastoma multiforme", once as Neuro-Behçet. The disease progressed over a course of 2--10 years from the initial ophthalmic symptoms to death. A review of the literature is given and the differential-diagnosis to necrotizing forms of retinitis, dissiminated chorioiditis neoplastic processes of retina and uvea and degenerative diseases are discussed. The primary reticulum-cellsarcoma of the retina must be considered in the differential-diagnosis of uveitis or panuveitis if 1. there is progression in spite of the usual antiinflammatory therapy, 2. the initial infiltrations are seen in the deep layers of the sensory retina.

Adult

Islet cells as a component of pancreatic ductal neoplasms. I. Experimental study: ductular cells, including islet cell precursors, as primary progenitor cells of tumors.

The ductular complex of the Syrian hamster pancreas represents a system of conduit which encompasses intercalated (intralobular), periinsular, and intrainsular ductules. The intercalated (intralobular) ductules comprise centroacinar and intercalated cells. A meshwork of small ductules (invisible by usual histologic procedures) surrounds islets (periinsular ductules) and extends in the form of often ramified tiny channels within the islet (intrainsular ductules). Although the function of the latter ductules is obscure, their cells seem to make up one of the undifferentiated cellular units of the pancreas, and as such are also the progenitors of beta-cells of the islets (islet cell precursor = IP). Systematic histologic examination of the pancreas in this species treated with pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine indicated that ductular cells, especially those of periinsular and intrainsular origin, are the most responsive to this carcinogen. The neoplastic process was initiated with hyperplasia of intercalated (intralobular) ductular and interlobular ductal cells associated with newly formed islets (nesidioblastosis). This process was followed by excess formation of mature but especially of immature islet cells and their precursors (IP) in the islet periphery, as well as with the appearance, distention, and multiplication of periinsular and particularly of intrainsular ductules. The hyperplasia, metaplasia, and malignant alteration of these periinsular and intrainsular ductules (including IP) and, to a lesser degree, of intercalated ductules indicated their histogenetic relationship and their potency for reproducing embryonic tissue on carcinogenic stimulus. The similarity of some induced lesions to diabetes has been emphasized.

Animals

Organ and tumor specificity of colon mucoprotein antigen in a rat model.

We purified a high-molecular-weight colon mucoprotein antigen (CMA) from normal F344 rat colon and from a transplantable dimethylhydrazine-induced colon carcinoma. Chemical analysis of the mucins showed similar amino acid and carbohydrate compositions. This finding was in contrast to the major differences that occurred in the composition of human CMA as a consequence of neoplasia. Immunohistochemical techniques were used in an examination of organ and tumor specificities. A New Zealand White rabbit antiserum against purified normal rat CMA, appropriately absorbed, detected a normal colon-specific determinant(s). The organ-specific determinant was lost as a consequence of neoplasia. However, a new tumor-specific determinant was then detected. CMA may have a potential role as an organ-specific marker of the neoplastic process.

Amino Acids

Peripheral blood lymphocyte nucleoi of rats with Yoshida ascitic sarcoma and the effect of endotoxin.

Nucleoli of lymphocytes were studied in the peripheral blood of male Wistar rats bearing Yoshida ascitic tumor untreated and treated with Escherichia coli endotoxin. Both the neoplastic process and the endotoxin produced an increase of peripheral lymphocytes with "active" nucleoli in number. The treatment of experimental animals bearing the tumor with the endotoxin decreased their mortality and enhanced the increase of the lymphocytes with "active" nucleoli in their peripheral blood.

Animals

[Functional activity of the lymphocytes of mouse lymph nodes in a system of viral carcinogenesis].

A study was made of the PHA-induced lymphocyte blastransformation (BT), and lymphocyte antitumor activity, using a model of progressive and regressive neoplastic process induced by the Moloney virus in mice BALB/c. The antitumor acitvity of lymphocytes was estimated by their ability to inhibit spheroid production by tumor cells. A lymphocyte BT and their antitumor activity was registered during a progressive growth of the tumor and its restoration as the tumor is regressing.

Animals

[Comparative ultrastructural study of the epithelial stromal junction in the prostatic gland].

In this paper, the authors carry out a comparative study of the structures adjacent to the alveolar periphery of the prostate-glands of men, dogs and bulls. In the three cases an E.S.J. (Epithelial-Stromal-Junction) similar to that described in the mammary gland and characterized in the first two cases by the existence of four, ultrastruct strata, consisting of the basal lamina, the somas of the adjacent fibroblasts and their cytoplasmic expansions as well as the arrangement of the intercellular, collagen microfibrils, was found to exist in this gland. In the case of the bovine prostate gland, the structural organization of the E.S.J. was basically characterized by the structural arrangement of the collagen microfibrils. The structures described constitute models on which to base future research on the hyperplastic and neoplastic processes of the prostate gland.

Age Factors

[Progressive multifocal encephalitis (PML)].

In four cases of progressive multifocal leucoencephalitis the basic disease was always a malignant lymphogranuloma. Changes in the brain were multifocal, however the frontoparietal area of the white matter was affected most frequently and foci in this part were oldest. In these foci demyelination with atypical astrogliosis predominated, and there was a very small number of scavenger cells. At the periphery of foci always proliferation and enlargement of homogenous oligodendroglia nuclei were found sometimes with inclusions which in immunoassay sometimes had a common antigen with papovirus SV 40 and on electronoptic examination always contained many virions of the papovirus. No direct relationship was found between the duration of the neoplastic process, its type and changes in the CNS.

Adult